The long-term objective of this project is to systematically investigate the regulation of choroidal blood flow and the role of the choroid in ocular pressure homeostasis. Ischemic damage is thought to be the underlying cause of blindness in ocular diseases such as diabetic retinopathy and glaucoma. Because the choroid is the primary source of oxygen and nutrients for the retina, knowledge of choroidal blood flow regulation is essential for understanding, preventing and treating the vascular consequences of these diseases. The current view of the choroid is that it is a passive vascular bed devoid of autoregulatory ability. However, this conclusion is based on the linear pressure-flow relation obtained when the perfusion pressure is decreased by raising the intraocular pressure. Studies in this laboratory show that elevated intraocular pressure is not the appropriate stimulus to elicit autoregulation in the choroid, and that choroidal blood flow is well autoregulated when arterial pressure is the manipulated variable. Moreover, by controlling the choroidal blood flow (and presumably blood volume), the mechanism responsible for choroidal autoregulation also regulates intraocular pressure. Therefore, this project will re-examine the issue of choroidal blood flow regulation by testing the following hypotheses: 1) a myogenic mechanism regulates the flow and volume of blood in the choroid, 2) the myogenic mechanism is modulated by neurohumoral factors, and 3) the myogenic mechanism plays a significant role in regulating intraocular pressure. Based on these hypotheses, a mathematical model of the choroid has been created to serve as the conceptual framework for the project. Because quantitative information for many of the model's key variables and relationships is not available in the literature, verifying the model's qualitative assumptions and reconciling its inconsistencies provide a logical basis for the project's specific aims which are: 1) to quantitate the local, neural and humoral control of choroidal blood flow to determine the normal myogenic set-point and the physiologic variables that modulate it, 2) to determine the role of the choroid in intraocular pressure by quantitating the compliances of the choroid and the ocular chambers, by measuring the vascular pressure gradients within the choroid, and by determining the factors that effect choroidal blood volume, and 3) to assess the effect of ocular hypertension on choroidal blood flow regulation in an animal model of glaucoma (i.e., trabecular obstruction) and to develop an animal model of glaucoma by shifting the myogenic set-point. All of the experiments will be conducted in anesthetized, albino rabbits artificially respired with room air and appropriately instrumented to control and monitor arterial and intraocular pressure while measuring choroidal blood flow by laser-Doppler flowmetry. The results of each series of experiments will be used to refine the mathematical model so that upon completion of the project the model will accurately portray the regulation of choroidal blood .flow and its role in ocular pressure homeostasis.